Barrett’s oesophagus is a premalignant metaplastic mucosa that is highly proliferative and characterised by mucosal instability (Hong et al. 1995). In the last two decades there has been a dramatic increase in the incidence of Barrett’s oesophagus and associated oesophageal adenocarcinoma in western populations (Blot et al. 1991). Factors associated with its development and malignant progression are poorly understood. Gastrin has a complex role in the regulation of epithelial cell proliferation and differentiation of gastrointestinal mucosa, primarily mediated through the classical COOH-terminally amidated peptides (Dockray, 1999). Gastrin has also been implicated as a mitogen for a number of GI and extra-GI tumours (Rehfeld et al. 1989; Nemeth et al. 1993). The aim of this study was to determine whether gastrin could influence cellular events in Barrett’s oesophagus.

Four patient groups were identified: control, reflux disease, Barrett’s metaplasia and adenocarcinoma. Endoscopic biopsies were collected from 3Ð5 cm above the gastro-oesophageal junction (GOJ) and 12Ð15 cm above the GOJ or 3 cm above the upper limit of the Barrett’s mucosa. The receptor was identified by RT-PCR and quantified by Northern analysis. [¹²⁵I]-G17-autoradiography was used to localise the CCK₂ receptor in frozen sections of Barrett’s mucosa. [³H]-thymidine and BrdU incorporation were used to determine proliferation in response to G17 in Barrett’s mucosal biopsies incubated ex vivo. The Salford and Trafford, and the Mersey Research Ethics Committees granted ethical approval for the study. All patients provided written informed consent.

Reverse transcription polymerase chain reaction (RT-PCR) identified expression of the CCK₂ receptor in the lower and mid-oesophagus in 3 of 8 controls (37 %), 5 of 7 patients with oesophagitis (71 %), 10 of 10 patients with Barrett’s metaplasia (100 %) and 7 of 12 patients with oesophageal adenocarcinomas (58 %). By Northern analysis a 2.1 kb mRNA, compatible with the CCK₂ receptor, was identified in PCR-positive samples. [¹²⁵I]-G17 bound to columnar epithelial cells within the glandular and lower crypt regions of Barrett’s mucosa. In experiments examining proliferation of Barrett’s mucosa incubated ex vivo, 10 nM G17 induced a 2-fold (n = 7, P = 0.0257, unpaired t test) increase in [³H]-thymidine incorporation at 24 h. This response was abolished by the addition of 100 nM of the specific CCK₂ receptor antagonist L-740, 093.

In summary, expression of the CCK₂ receptor appears to be related to the degree of mucosal inflammation, with mRNA for the receptor present in a greater number of patients with Barrett’s/reflux oesophagitis compared with controls. CCK₂ receptor mRNA is ubiquitously expressed in Barrett’s mucosa with the receptor located on epithelial cells within the proliferative zone of the tissue. Amidated gastrin can be shown to induce proliferation in Barrett’s mucosa via the CCK₂ receptor.

All procedures accord with current local guidelines and the Declaration of Helsinki.